Knoevenagel condensation reactions catalysed by metal-organic frameworks

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Catalysis Letters ISSN 1011-372XVolume 143Number 6 Catal Lett (2013) 143:563-571DOI 10.1007/s10562-013-0995-5

Knoevenagel Condensation ReactionsCatalysed by Metal-Organic Frameworks

Andrew R. Burgoyne & ReinoutMeijboom

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Knoevenagel Condensation Reactions Catalysedby Metal-Organic Frameworks

Andrew R. Burgoyne • Reinout Meijboom

Received: 6 February 2013 / Accepted: 17 March 2013 / Published online: 30 March 2013

� Springer Science+Business Media New York 2013

Abstract Functionalised metal-organic frameworks (MOFs)

which contain amino groups on their secondary building

units (SBUs) are basic catalysts in the Knoevenagel con-

densation. University of Michigan Crystalline Material-1-

amine (UMCM-1-NH2), Isoreticular MOF-3 (IRMOF-3)

and a 5 % IRMOF-3 mixed in Isoreticular MOF-1 (MI-

XMOF) were evaluated as solid basic catalysts and dem-

onstrated to be more active than aniline, their homogenous

anologue. UMCM-1-NH2’s performance was higher than

that of the other MOFs studied. IRMOF-3 and MIXMOF

proved to have equal catalytic ability. Their catalytic per-

formance was monitored at various temperatures and in

different solvents for the reaction between benzaldehyde

and ethyl acetoacetate or ethyl cyanoacetate.

Keywords Heterogeneous catalysis � Catalysis activity �Elementary kinetics � C–C coupling � Organic chemicals

and reactions

1 Introduction

The potential use of porous base catalysts in fine chemical

production is enormous [1–3]. Base-catalysed condensation

and addition reactions are some of the more important

reaction steps employed for building large and complex

molecules, characteristic of the fine chemical and phar-

maceutical industries. The replacement of liquid organic

bases such as piperidine, as well as alkali metal hydroxides,

with solid base catalysts could lead to an easier separation

of catalyst from the product stream, and thus to a cleaner

production. In addition, heterogeneous catalysts are known

to suppress side reactions such as self-condensation and

oligomerization, resulting in better selectivity and reaction

conversion.

The Knoevenagel condensation occurs between a C=O

group and an activated methylene group. This C–C bond

coupling reaction is useful within the drug industry where

important intermediates are prepared. In addition, it is

employed as a classic test reaction to analyse the activity of

a variety of solid base catalysts. The hydrogens in

b-dicarbonyl compounds have typical pKa values in the

range 9–11 [4]. This makes them ideal substrates for test-

reactions utilizing a Knoevenagel condensation. Com-

pounds with active methylene groups, with different pKa

values can be reacted with belzaldehyde to test the

strength of a basic catalyst. A robust study using IRMOF-3

was reported previously using ethyl cyanoacetate (pKa *9)

and ethyl acetoacetate (pKa *10.7) with benzaldehyde

[5].

Here we report on the Knoevenagel condensation

between benzaldehyde and ethyl cyanoacetate or ethyl

acetoacetate as catalysed by the primary amines embedded

inside the well-known metal-organic framework IRMOF-3

[6]. Initial catalyst evaluation resulted in a set of optimized

conditions that was expanded to other MOF frameworks,

namely MIXMOF [7] and UMCM-1-NH2 [8]. All reactions

were compared against the homogeneous counterpart uti-

lizing aniline as the catalyst.

Electronic supplementary material The online version of thisarticle (doi:10.1007/s10562-013-0995-5) contains supplementarymaterial, which is available to authorized users.

A. R. Burgoyne � R. Meijboom (&)

Research Centre for Synthesis and Catalysis, Department of

Chemistry, University of Johannesburg, PO Box 524, Auckland

Park, Johannesburg 2006, South Africa

e-mail: [email protected]

123

Catal Lett (2013) 143:563–571

DOI 10.1007/s10562-013-0995-5

Author's personal copy

http://dx.doi.org/10.1007/s10562-013-0995-5

2 Experimental

2.1 General Experimental

All chemicals were purchased from Sigma-Aldrich and used

as received. GC runs were performed on a Shimadzu

GC-2010-Plus with an auto injector (AOC-20i), auto sam-

pler (AOC-20s) and a 30 m RTX�-5 fused silica capillary

column. The synthesis of IRMOF-3 [6], MIXMOF [7] and

UMCM-NH2 [8] was performed according to literature

procedures. All characterisation data were in agreement with

literature (see supplementary material).

2.2 Catalytic Runs

All catalytic runs were performed in a similar manner. A

representative example is given here. A given amount of the

amino containing catalyst, corresponding to 0.2 mmol –NH2,

was added to a solution of ethyl acetoacetate or ethyl cya-

noacetate (7 mmol) in solvent (5 cm3) in a round bottom flask

(50 cm3). The reactor was encapsulated in a water jacket for

temperature control, while being shaken under an inert atmo-

sphere (N2) to avoid oxidation. After temperature equilibrium

was reached, benzaldehyde was added (8 mmol) while keep-

ing the reaction mixture under a static nitrogen atmosphere.

The reaction mixture was sampled at predetermined time-

intervals. A 40 ll sample was diluted with CH2Cl2 (1.9 cm3)

and of this mixture 0.5 ll was injected into the GC. The

analysis was performed immediately after sampling to avoid

any additional conversion in the reaction mixture.

2.3 Computational Details

The averages of triplicate catalytic runs were modelled onto

a line of best fit using the equation y = -A e(-Rx) ? c using

Kinetic Studio. The gradient of these exponential slopes

provided the kobs for each catalytic run with a corresponding

standard deviation. Manipulation of these provided infor-

mation to calculate the activation energy from the Arrhenius

equation and the enthalpy and entropy from the Eyring Plot.

An ANOVA statistical analysis, using Microsoft Excel 2010,

was performed on the final conversion of the homogenous vs

heterogeneous, solvent and temperature studies to statisti-

cally analyse their differences. A Student’s t test was per-

formed on the final conversion of the MeOH/EtOH at 353

and 333 K, the order of addition of substrates and different

substrates studies to compare two different variables.

3 Results and Discussion

The Knoevenagel condensation, of aldehydes with com-

pounds containing activated methylene groups, is a robust

reaction often used to test catalytic abilities of basic cata-

lysts [9] and in the production of fine chemicals as well as

heterocyclic compounds of biological significance [10].

Conventionally, this reaction is catalysed by alkali metal

hydroxides or by homogeneous organic bases like primary,

secondary and tertiary amines [11]. However, recycling

and catalyst recovery are problems which arise from their

use.

The amine catalysed Knoevenagel condensation reac-

tion, Scheme 1, involves the nucleophilic attack of the

amine onto the methylene substrates resulting in a carbo-

cation intermediate. The carbo-cation intermediate then is

involved in a nucleophilic addition with benzaldehyde

resulting in the formation of the product and water with

100 % selectivity and regeneration of the amine catalyst.

The metal-organic frameworks IRMOF-3, UMCM-1-

NH2 and MIXMOF were tested as potential basic catalysts

in the Knoevenagel condensation reaction between benz-

aldehyde and different methylene substrates in a range of

solvents at different temperatures. Initial tests were per-

formed using diethyl malonate which has a pKa of 13.3 and

benzaldehyde utilizing IRMOF-3 as the catalyst. The pKa

of this substrate, however, proved to be too high and only

1.6 ± 0.9 % of the diethyl malonate was converted to the

desired product after 130 min in DMSO at 318 K. The

reaction was allowed to continue up to 20 h where it

revealed that only 5.9 ± 1.1 % conversion was achieved

with 100 % selectivity.

Subsequently, ethyl acetoacetate was utilized as a sub-

strate, with a pKa of 10.7. The lowered pKa resulted in

increased conversion. In the absence of a catalyst, some

product formed (3.9 ± 1.8 %), similar to the reaction using

diethyl malonate as a substrate (1.6 ± 0.9 %). A compar-

ison was thus performed to analyse the performance of

IRMOF-3, a porous heterogenous catalyst, against aniline,

a homogenous analogue similar to that found within the

MOF structure.

The products of the Knoevenagel condensation between

benzaldehyde and ethyl acetoacetate were characterized

using conventional spectroscopic techniques. Filtration, to

remove the IRMOF-3 catalyst, and subsequent removal of

the solvent in vacuo resulted in a clean product. Conven-

tional FT-IR and NMR analyses on the yellow oil obtained

confirmed the presence of the proposed condensation

product.

FT-IR analysis of the substrates, benzaldehyde and ethyl

acetoacetate, and product gave vital information about the

recognition of their disappearance of substrates and the

appearance of the product. The product showed identifiable

absorption peaks at mC=C = 1,624 cm-1 for the newly

formed C=C bond; mC=O = 1,727 and 1,705 cm-1 for the

b-dicarbonyl system which shifted from mC=O = 1,737 and

1,713 cm-1 in ethyl acetoacetate; m=C–H = 2,995 cm-1

564 A. R. Burgoyne, R. Meijboom

123


and d=C–H = 696 cm-1 for the newly formed proton on the

alkene; mC–O–C = 1,044 cm-1 which shifted from mC–O–C =

1,040 cm-1 in ethyl acetoacetate. The product showed an

absence of peaks in the region 2,720–2,850 cm-1 typical for

the methylene hydrogens in ethyl acetoacetate, m=C–H =

2,984 cm-1. Also absent in the product were m=C–H = 2,818

and 2,737 cm-1 and mC=O = 1,698 cm-1, which represent

the benzaldehyde’s carbonyl hydrogen and the carbonyl.1H NMR analysis of the reaction mixture was performed

at the start of a reaction and then again upon completion of

the 130 min. The singlet at 10.13 ppm (CHO) for benzal-

dehyde was of lower intensity than that of the peaks of the

product. New absorbance peaks at 1.29 ppm (t, 3H, CH3,

J = 6.8 Hz), 2.39 ppm (s, 3H, CH3), 4.28 ppm (q, 2H,

CH2, J = 7.2 Hz), 7.34–7.40 ppm (m, 3H, CH), 8.01 ppm

(d, 2H, CH) and 8.40 ppm (s, 1H, C=CH) were present,

confirming the presence of the product.

The heterogeneous catalyst, IRMOF-3, gave significantly

higher conversion rates in DMSO at 353 K and was faster,

kobs = (6.71 ± 1.21) 910-2 s-1, than the homogenous

equivalent, aniline which had a kobs = (0.30 ± 0.01)

910-2 s-1, even with the amount of amino groups being

equal in both cases (Table 1). Aniline closely resembles the

2-aminoterephthalic acid which contains the amino group

within the MOF material. Gascon et al. [5] also observed a

similar trend when working with ethyl cyanoacetate in

DMSO. This indicates that the reactivity of the amino groups

is increased by being contained within the MOF structure. In

the absence of a catalyst only 3.9 ± 1.8 % of the substrates

were converted to product, kobs = (0.00 ± 0.17) 910-2 s-1.

The turn-over-frequencies (TOFs) given are based on the

initial data points (10 min into reaction) and based on the

assumption that all –NH2 groups are catalytically active cen-

tres, no matter how deep within the porous MOF network.

3.1 Optimization of Reaction Conditions

A range of conditions could potentially influence the

Knoevenagel condensation reaction. Thus, in order to be

able to compare the various potential catalysts, we opti-

mized the conditions for IRMOF-3. Subsequently, the

different MOF materials were compared under optimized

conditions. The following parameters were studied: solvent

dependence, temperature and order of addition.

A solvent dependence study was performed at 353 K to

determine which factors would influence the activity of the

catalysts. The reaction rate of a homogenous basic catalyst

depends on several aspects, including:

• Polarity: when polar reagents are involved, the transi-

tion-state complex is better able to be solvated by polar

solvent molecules. This behaviour of the solvent influ-

encing the transition state is accounted for in the ability of

the catalyst to transfer protons. The general rule is that the

more polar solvents show higher reaction rates [12, 13].

• Amphiprotic properties: a protic solvent (i.e. ethanol or

methanol) might also increase the activation of the slightly

basic benzaldehyde, resulting in higher activities.

The solvents selected, for solvent dependence study of

the MOF catalysed reaction between benzaldehyde and

ethyl acetoacetate, were solvents with a range of dielectric

constants (e): DMSO (e = 48.9), DMF (e = 36.7), MeOH

H

O

O

O O

O

O

CN

O

O O

O

O

CN

H2O

(i)

(ii)

(ii)

(i)

NH2

NH3O

O O

O

O

CN

(i)

(ii)

O

O O

O

O

CN

(ii)

(i)

O

O

+

Scheme 1 Catalytic cycle for

Knoevenagel condensation

between benzaldehyde and

i ethyl acetoacetate or ii ethyl

cyanoacetate, catalysed by a

primary amine as contained in

the MOF materials

Knoevenagel Condensation Reactions 565

123


(e = 33), EtOH (e = 24.3) and toluene (e = 2.4). Solvents

with higher dielectric constants were assumed to have a

higher polarity.

The results for the solvent dependence study are shown

in Fig. 1 where benzaldehyde was reacted with ethyl ace-

toacetate at 353 K in 5 cm3 of different solvents with IR-

MOF-3 as a catalyst. DMSO, with the highest dielectric

constant, had the highest conversion of 64.5 % ± 4.4 with

kobs = (10.53 ± 0.52) 910-2 s-1. This can be explained

by the hydrogen bond acceptor power of DMSO, which

stabilises the –NH2 group in the protonated form, and thus

increases the rate of proton transfer [12] from the methylene

substrate to the amine catalyst. As a result, the intermediate

is stabilized by the more polar solvents. In all runs, typical

first order kinetic plots were obtained, as shown in Fig. 1.

The calculated rates of reaction, kobs, for the various sol-

vents studied in the Knoevenagel condensation of benzal-

dehyde and ethyl acetoacetate at 353 and 333 K catalysed by

IRMOF-3 are listed in Table 2.

The hydrophilic character of a catalyst support determines

the performance of supported homogeneous catalysts [5, 10].

A relationship occurs such that: the higher the hydrophilicity

of the catalyst support, the lower the effect of the solvent and

thus the faster diffusion can occur within the material. Not all

Zn atoms in IRMOF-3 are fully coordinated [9], i.e. have a

full coordination sphere, resulting in IRMOF-3 being a

hydrophobic catalyst support. Hence, a large effect on the

catalytic ability of many Zn based MOFs is due to the effect

of solvents. However, it was noted that at 353 K in the more

polar solvents the amount of catalyst able to be recycled, by

filtration and washing with fresh DMF, was significantly less

than in solvents with lower polarities. Nguyen et al. [14]

showed that zeolite imidazolate frameworks (ZIFs), a novel

subclass of MOFs, also suffers from a decrease in the crystal

size, in THF (e = 7.6), due to the crystals breaking into small

fragments. Thus, a sacrificial balance between activity and

recyclability needs to be made.

Figure 1 also showed similar activities for both MeOH

(Table 2, entry 3) and EtOH (Table 2, entry 4) at 353 K,

which was notably above each of their boiling points under

atmospheric pressure. To achieve these observations the

reaction vessel was fitted with a reflux condenser while

being capped to conserve the static nitrogen atmosphere.

A second evaluation of MeOH (Table 2, entry 6) and EtOH

(Table 2, entry 7) as solvents was performed, this time at

333 K, which is lower than each of the solvents’ boiling

points. A similar trend to what was previously seen was

observed again at the lower temperatures, being that the more

Table 1 Reaction conversions, calculated kobs values and TOFs for solvents studied in Knoevenagel condensation of benzaldehyde and ethyl

acetoacetate catalysed by IRMOF-3, aniline and without catalyst in DMSO at 353 K

Catalyst Solvent Temperature (K) Reaction conversion (%) kobs (10-2 s-1) Initial TOF (min-1)

IRMOF-3 DMSO 353 64.5 ± 4.4 67.08 ± 12.08 0.44

Aniline 28.0 ± 3.6 3.00 ± 0.99 0.02

No catalyst 3.9 ± 1.8 0.00 ± 1.65 –

Fig. 1 Knoevenagel

condensation of benzaldehyde

and ethyl acetoacetate in DMSO

(filled diamond); DMF (filledsquare); MeOH (filled triangle);

EtOH (white circle) or toluene

(times) at 353 K catalysed by

IRMOF-3; n = 3 repeats


123


polar solvent, MeOH, showed a higher activity with a con-

version of 53.5 ± 2.2 % and kobs = (4.76 ± 0.50) 9

10-2 s-1. It was also noted that the conversion in MeOH was

raised at 333 K, in comparison to the conversion at 353 K. The

conversion in EtOH at 333 K, 34.7 ± 4.5 %, was lower than

its conversion at 353 K, 42.3 ± 1.4 %. However the rate of

reaction was faster, kobs = (6.96 ± 0.92) 910-2 s-1, at

353 K than at 333 K where kobs = (2.32 ± 0.55) 910-2 s-1.

Studies at 353, 333 and 313 K (Table 1, entries 8–10)

were performed on the Knoevenagel condensation between

benzaldehyde and ethyl acetoacetate in DMF under a static

nitrogen atmosphere catalysed by IRMOF-3. DMF was

selected as the best solvent even though DMSO showed

higher activities at 353 K, but it was observed that the

amount of catalyst which could be recovered, by filtration

and washing with fresh DMF, after a catalytic run was

higher in DMF than it was in DMSO. Thus a sacrifice

between activity and recyclability was made in the aim to

optimise the catalytic reaction conditions of the catalyst.

Catalytic reactions performed at 353 K not only gave

higher conversions, 54.0 ± 0.0 % within the 130 min

where the reaction was monitored, but also a higher

kobs = (9.58 ± 0.43) 910-2 s-1 was observed. At 333 K,

a lower temperature, a lower conversion of 39.0 ± 1.4 %

was obtained with a kobs = (2.11 ± 0.20) 910-2 s-1. The

lowest temperature studied, 313 K, resulted in a conversion

of 27.7 ± 4.3 % with a kobs = (0.51 ± 0.38) 910-2 s-1.

To ascertain as to whether the order of addition was

important in the Knoevenagel reaction, between benzalde-

hyde and ethyl acetoacetate catalysed by IRMOF-3 in DMF

at 313 K, a comparative reaction was performed where the

ethyl acetoacetate (Table 2, entry 12) was added first as

opposed to the addition of benzaldehyde first (Table 2, entry

11). This was performed to rule out the concept of the for-

mation of amides, where the ethyl acetoacetate would react

with the benzaldehyde, which would thus deactivate the

catalyst. No significant difference in the percent conversion

was observed in the catalytic ability of IRMOF-3. Gascon

et al. [5] similarly saw this occurring in the Knoevenagel

catalysed reaction of ethyl cyanoacetate and benzaldehyde.

A higher conversion might be expected when benzalde-

hyde is added first, as this would inhibit the formation of the

deactivating amides. However, this was not observed and the

conversion achieved by adding ethyl acetoacetate first was

27.7 ± 1.9 % with kobs = (0.51 ± 0.38) 910-2 s-1, where

upon adding the benzaldehyde first the conversion attained

was 27.6 ± 2.8 % with kobs = (0.52 ± 0.41) 910-2 s-1.

From the Arrhenius equation the activation energy, Ea,

can be calculated and states that:

k ¼ Ae�EaRT

where k is the observed rate constant (s-1), A the pre-

exponential factor, Ea the activation energy (J mol-1),

R the Universal gas constant (8.3144621 J mol-1 K-1) and

T the temperature (K). Thus a plot of 1/T versus ln kobs

produces a straight line where the product of the gradient

and the Universal gas constant equate to the Ea.

From the Eyring-Polanyi equation the enthalpy, DH, and

entropy, DS, can be calculated and states that:

k ¼ kbT

he�DG�

RT

where k is the observed rate constant (s-1), kb the Boltzmann

constant (1.3806488 9 10-23 J K-1), T the temperature

Table 2 Reaction conversions, calculated kobs and TOFs for the Knoevenagel condensation of benzaldehyde and ethyl acetoacetate catalysed by

IRMOF-

Run Solvent Temperature (K) Reaction conversion (%) kobs (10-2 s-1) Initial TOF (min-1)

1 DMSO 353 64.5 ± 4.4 10.53 ± 0.52 0.44

2 DMF 54.0 ± 0.5 9.58 ± 0.43 0.39

3 MeOH 43.0 ± 5.2 7.38 ± 1.07 0.22

4 EtOH 42.3 ± 1.4 6.96 ± 0.92 0.29

5 Toluene 15.8 ± 2.4 1.17 ± 0.55 0.15

6 MeOH 333 53.5 ± 2.2 4.76 ± 0.50 0.39

7 EtOH 34.7 ± 4.5 2.32 ± 0.55 0.29

8 DMF 353 54.0 ± 0.0 9.58 ± 0.43 0.39

9 DMF 333 39.0 ± 1.4 2.11 ± 0.20 0.27

10 DMF 313 27.7 ± 4.3 0.51 ± 0.38 0.10

11 DMFa 313 27.6 ± 2.8 0.52 ± 0.41 0.10

12 DMF 313 27.7 ± 1.9 0.51 ± 0.38 0.08

For all runs, the solvent volume was 5 cm3 and the values are the average of n = 3 repeats. Reaction conversions are reported at the end of the

run (130 min)a Benzaldehyde added first


123


(K), h the Planck’s constant (6.62606957 9 10-34 J s), DG*

the Gibbs energy of activation (J mol-1), R the Universal gas

constant (8.3144621 J mol-1 K-1) and T the temperature

(K). Thus a plot of 1/T versus ln (k/T) produces a straight line

with gradient equal to –DH/R and with a y-intercept of ln

(kb/h) ? DS/R.

The aforementioned plots were performed and Ea was

found to be 973 J mol-1, DH was calculated as 933 J mol-1

and DS as -84 J K-1 mol-1 for the IRMOF-3 catalysed

Knoevenagel condensation of benzaldehyde and ethyl ace-

toacetate in DMF.

3.2 Comparative Reactions Using IRMOF-3, UMCM-

1-NH2 and MIXMOF

The ability of these basic MOFs to deprotonate different

methylene hydrogens was tested in the Knoevenagel cata-

lysed reaction between benzaldehyde and diethyl malonate

(pKa *13.3 [15]); ethyl acetoacetate (pKa *10.7) and

ethyl cyanoacetate (pKa *9.0 [16]) at 313 K in DMF. In

most cases, the Knoevenagel reaction is used as a test

reaction to shed light on the catalytic abilities of basic

solids, particularly MOFs and zeolites [6].

None of the MOF materials were able to catalyse the

Knoevenagel reaction between benzaldehyde and diethyl

malonate with any significant conversion, as the pKa was

too high for the –NH2 groups present in the MOF. Selecting

a different substrate, ethyl acetoacetate, resulted in lowering

the pKa of the substrate from 13.3 to 10.7 allowed for sig-

nificantly higher results as shown in Table 3, which could

then be used for comparison of the different MOF catalysts.

For IRMOF-3 it was observed that only 1.2 ± 0.4 %

conversion was achieved when reacting diethyl malonate

with benzaldehyde; 27.7 ± 2.8 % conversion could be

achieved when reacting ethyl acetoacetate with benzalde-

hyde and 73.1 ± 1.6 % could be achieved when reacting

ethyl cyanoacetate with benzaldehyde after 130 min at

313 K in DMF. The difference in conversions is large, due

to the various strengths of the C–H bond of the methylenes

in the different substrates.

For the same catalyst loading, as in IRMOF-3, a large

mass of MIXMOF was required. To provide 0.18 mmol –

NH2 in IRMOF-3 only 36 mg is required. However, for

Table 3 Reaction conversions, calculated kobs and TOFs in Knoevenagel condensation of benzaldehyde and ethyl acetoacetate or ethyl cya-

noacetate or diethylmalonate catalysed by IRMOF-3, UMCM-1-NH2 and MIXMOF

Run Substrate Catalyst Solvent Temperature

(K)

Reaction

conversion (%)

kobs

(10-2 s-1)

Initial TOF

(min-1)

Reference

Ethyl acetoacetate UMCM-1-NH2 44.0 ± 3.4 3.04 ± 0.23 1.01

1 IRMOF-3 DMF 27.7 ± 2.8 0.46 ± 0.40 0.10 This work

MIXMOF 30.0 ± 2.1 0.55 ± 0.38 0.07

Ethyl cyanoacetate UMCM-1-NH2 73.1 ± 1.6 11.58 ± 0.13 2.02

2 IRMOF-3 DMF 62.3 ± 1.7 2.87 ± 0.24 1.21 This work

MIXMOF 62.9 ± 3.2 3.26 ± 0.22 1.13

3 Diethyl malonate IRMOF-3 DMF 1.2 ± 0.4 – – This work

4 Ethyl cyanoacetate IRMOF-3 DMSO 313 99 – 2.9 [5]

5 Ethyl acetoacetate IRMOF-3 DMSO 353 58 – 0.33 [5]

6 Ethyl cyanoacetate Ethyldiamine

grafted MIL-101

Cyclo

hexane

353 80 – 0.37 [17]

7 Ethyl acetoacetate BEA Xylene 403 82 – – [18]

8 Ethyl acetoacetate TS-1 Xylene 403 41 – – [18]

9 Ethyl acetoacetate CuBTC Xylene 403 40 – – [18]

10 Ethyl acetoacetate FeBTC Xylene 403 58 – – [18]

11 20-hydroxyacetophenone

SBA-NH2-10-P DMSO 413 52 – – [19]

12 C6H5–

NO2

413 53 – – [19]

13 C6H5–CN 413 35 – – [19]

14 Hexyl

alcohol

413 12 – – [19]

15 1,3,5-

CH3–

C6H3

413 55 – – [19]

16 – 413 84 – – [19]

Solvent DMF, n = 3 repeats


123


MIXMOF, as the percentage of ABDC is only 5 % amongst

the organic linkers, 720 mg MIXMOF is required to supply

0.18 mmol –NH2. This increase in mass made using

MIXMOF, as a catalyst, less desirable than IRMOF-3, as

twenty times the mass is required and the conversion of ethyl

cyanoacetate at 313 K in DMF was only 62.9 ± 3.2 % after

130 min. This was significantly larger than the conversion of

ethyl acetoacetate, which only achieved 30.0 ± 2.1 % at

313 K in DMF after 130 min. MIXMOF and IRMOF-3 both

have similar catalytic abilities to catalyse the Knoevenagel

reaction between ethyl acetoacetate or ethyl cyanoacetate

and benzaldehyde.

It is of note that UMCM-1-NH2, with a larger surface

area and pore sizes, in both cases provided the highest

Fig. 2 Knoevenagel

condensation of benzaldehyde

and ethyl cyanoacetate (dasheddotted line) or ethyl

acetoacetate (dotted line) in

DMF at 313 K catalysed by

UMCM-1-NH2 (filled triangle);

MIXMOF (filled square);

IRMOF-3 (filled diamond);

n = 3 repeats

Table 4 Reaction conversions, calculated kobs and TOFs in Knoevenagel condensation of benzaldehyde and ethyl acetoacetate or ethyl cya-

noacetate catalysed by recycled IRMOF-3, UMCM-1-NH2 and MIXMOF

Run Catalyst Substrate Solvent Temperature (K) Reaction conversion (%)

1 UMCM-1-NH2 Ethyl acetoacetate DMF 313 44.0 ± 3.4

2 41.5 ± 2.7

3 39.9 ± 1.5

1 UMCM-1-NH2 Ethyl cyanoacetate DMF 313 73.1 ± 1.6

2 72.6 ± 2.1

3 70.4 ± 1.9

1 IRMOF-3 Ethyl acetoacetate DMF 313 27.7 ± 2.8

2 27.5 ± 1.8

3 25.8 ± 2.2

1 IRMOF-3 Ethyl acetoacetate DMF 313 62.3 ± 1.7

2 60.9 ± 2.3

3 60.1 ± 2.5

1 MIXMOF Ethyl acetoacetate DMF 313 30.0 ± 2.1

2 29.8 ± 1.8

3 27.6 ± 3.2

1 MIXMOF Ethyl acetoacetate DMF 313 62.9 ± 3.2

2 61.7 ± 2.7

3 59.2 ± 1.9

Solvent DMF, n = 3 repeats


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reaction rates with kobs = (11.58 ± 0.13) 910-2 s-1 for

the Knoevenagel condensation between ethyl cyanoacetate

and benzaldehyde and kobs = (3.04 ± 0.23) 910-2 s-1 for

ethyl acetoacetate and benzaldehyde. This large difference

in kobs, shown in Table 3, can be explained by the relative

ease by which the more acidic hydrogens of ethyl cya-

noacetate can be removed than the less acidic hydrogens of

ethyl acetoacetate. Of interest also are the similar yet

slightly larger kobs of MIXMOF, in both cases, compared to

that of IRMOF-3. This difference was analysed statistically

using the Student’s t test to compare the differences

between the data.

UMCM-1-NH2 also required a higher mass, than IRMOF-3,

of catalyst to keep the catalyst loading constant. Although in

this case only 144 mg UMCM-1-NH2 is needed to provide

0.18 mmol –NH2. The catalytic ability of UMCM-1-NH2

was higher than IRMOF-3 and MIXMOF. UMCM-1-NH2

resulted in a larger conversion, over the 130 min, of

44.0 ± 3.4 % in the reaction between benzaldehyde and

ethyl acetoacetate and of 73.1 ± 1.6 % in the reaction

between benzaldehyde and ethyl cyanoacetate. These con-

versions are competitive with literature results, as shown in

Table 3. IRMOF-3 has been shown to be able to achieve a

remarkable 99 % conversion of substrate in DMSO at 313 K

when ethyl cyanoacetate was used as a substrate and with

ethyl acetoacetate only 58 % was observed [5]. Ethyldi-

amine grafted MIL-101 yielded 80 % reaction conversion of

ethyl cyanoacetate at 353 K [17], which is higher than all the

observed reaction conversions in this study although the

solvent DMSO was used at 353 K, which was higher than the

studies performed on ethyl cyanoacetate. In the work of

Opanasenko et al. [18] BEA, TS-1, CuBTC and FeBTC were

shown to give 82, 41, 40 and 58 %, respectively, in the cat-

alysed reaction of benzaldehyde and ethyl acetoacetate at

403 K in xylene. Although, in this study IRMOF-3 and

MIXMOF did result in lower reaction conversions than the

study performed by Opanasenko et al., this is most likely due

to the temperature it was performed at, 313 K, as opposed to

403 K. Similarly, the amine containing SBA-15 zeolite was

shown to have basic catalytic abilities in catalysing the car-

bon coupling of the 20-hydroxyacetophenone and benzalde-

hyde, as shown in Table 3, in a variety of solvents. The

reaction conversions were of a similar magnitude to the

results obtained in this study, despite the lower surface

area of the zeolitic basic catalyst and the higher reaction

temperature, 413 K [19] (Fig. 2).

3.3 Recyclability

A large loss of mass, up to as much as half the mass in

some cases due to attrition and dissolution, of the hetero-

geneous catalyst at 353 K and DMSO as a solvent was

observed. Consequently, less harsh conditions were chosen

for the recyclability study. The Knoevenagel condensation

of benzaldehyde and ethyl acetoacetate in DMF at 313 K

showed similar results, as shown in Table 4, for the first

three catalytic runs. GC analysis to quantify reaction con-

version for recyclability studies were performed only at

130 min for comparison of each catalytic run after recy-

cling of the catalyst. Upon completion of a catalytic run,

the catalyst was filtered from the reaction mixture and

washed in DMF at 313 K overnight and then washed with

CHCl3. Activation of the catalyst and removal of CHCl3was achieved by drying the catalyst in a vacuum oven at

373 K at 560 mm Hg. Gascon et al. [5] also observed such

catalytic capabilities over the first three runs for IRMOF-3

in the Knoevenagel condensation of benzaldehyde and

ethyl cyanoacetate. Nguyen et al. [14] provided evidence

that for the first three catalytic runs ZIF-9 had the same

reaction rate in the Knoevenagel condensation of benzal-

dehyde and malononitrile.

4 Conclusions

In this study IRMOF-3, UMCM-1-NH2 and MIXMOF

were compared as basic heterogeneous catalysts in the

Knoevenagel condensation between benzaldehyde and

ethyl acetoacetate or ethyl cyanoacetate. IRMOF-3 was

found to yield higher conversion rates than the homoge-

neous analogue, aniline. This suggests the idea that the

basicity of the amine group within the MOF structure is

enhanced when within the MOF material [5].

UMCM-1-NH2 in all cases had higher catalytic activities

than IRMOF-3 and MIXMOF which had near identical

catalytic activities in all cases. Optimization of the reaction

conditions found that 353 K was the optimal temperature for

higher substrate conversion, but lower temperatures, 313 K,

allowed for better catalyst recovery. Substrates with lower

pKa values yielded high conversions. From the Arrhenius

equation it was found that Ea = 973 J mol-1 and from the

Eyring-Polanyi equation that DH = 933 J mol-1 and

DS = -84 J K-1 mol-1 for the IRMOF-3 catalysed Knoe-

venagel condensation between benzaldehyde and ethyl

acetoacetate.

Acknowledgments Funding from the South African NRF, Sasol

R&D and the research fund from the University of Johannesburg are

gratefully acknowledged. ARB is grateful to the NRF-DAAD for a

scholarship. Mr. D. Harris and Dr. R. Meyer (Shimadzu South Africa)

are acknowledged for use of their equipment.

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Knoevenagel condensation reactions catalysed by metal-organic frameworks

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